Human serum albumin undergoes a variety of conformational changes with changes in pH and upon binding various small molecules. These changes in conformation seem to result in an expansion and a drastic change in secondary and tertiary structure of the protein. We plan to extend these studies by examining the effects of other metabolites and drugs upon the structure of human serum albumin, and, in turn to examine how these structural changes affect the affinity of serum albumin for other molecules. We plan to use fluorescence energy transfer techniques to quantitate these changes in albumin structure by measuring distances between different regions of the albumin molecule in the presence and absence of small molecules which are found to expand serum albumin. These studies may show why binding of drugs or metabolites at one site of serum albumin affects binding of metabolites on another portion of the molecule.